Nanoparticle PET-CT Imaging of Macrophages in Inflammatory Atherosclerosis
Open accessAbstract
Background— Macrophages participate centrally in atherosclerosis, and macrophage markers (eg, CD68, MAC-3) correlate well with lesion severity and therapeutic modulation. On the basis of the avidity of lesional macrophages for polysaccharide-containing supramolecular structures such as nanoparticles, we have developed a new positron emission tomography (PET) agent with optimized pharmacokinetics to allow in vivo imaging at tracer concentrations. Methods and Results— A dextranated and DTPA-modified magnetofluorescent 20-nm nanoparticle was labeled with the PET tracer 64 Cu (1 mCi/0.1 mg nanoparticles) to yield a PET, magnetic resonance, and optically detectable imaging agent. Peak PET activity 24 hours after intravenous injection into mice deficient in apolipoprotein E with experimental atherosclerosis mapped to areas of high plaque load identified by computed tomography such as the aortic root and arch and correlated with magnetic resonance and optical imaging. Accumulated dose in apolipoprotein E–deficient aortas determined by gamma counting was 260% and in carotids 392% of respective wild-type organs ( P <0.05 both). Autoradiography of aortas demonstrated uptake of the agent into macrophage-rich atheromata identified by Oil Red O staining of lipid deposits. The novel nanoagent accumulated predominantly in macrophages as determined by fluorescence microscopy and flow cytometry of cells dissociated from aortas. Conclusions— This report establishes the capability of a novel trimodality nanoparticle to directly detect macrophages in atherosclerotic plaques. Advantages include improved sensitivity; direct correlation of PET signal with an established biomarker (CD68); ability to readily quantify the PET signal, perform whole-body vascular surveys, and spatially localize and follow the trireporter by microscopy; and clinical translatability of the agent given similarities to magnetic resonance imaging probes in clinical trials.
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Nahrendorf et al. labelled iron oxide nanoparticles with 64Cu, showing accumulation in atherosclerotic arteries of APOE-knockout mice using PET-CT.
“For example, Nahrendorf et al.148 labelled iron oxide nanoparticles with the radiolabelled PET tracer 64Cu, showing the accumulation of the nanoparticles in atherosclerotic arteries of APOE-knockout mice using PET–CT imaging (FIG. 6b).”
From Perspectives and opportunities for nanomedicine in the management of atherosclerosis (2011) · cites this paper as [148]
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Self-citation
- Authors
- Nahrendorf, M., Zhang, H., Hembrador, S., Panizzi, P., Sosnovik, D. E., Aikawa, E., Libby, P., Swirski, F. K., & Weissleder, R.
- Affiliations
- Brigham and Women's Hospital (US)
- From the Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston (M.N., R.W.); Center for Molecular Imaging Research, Massachusetts General Hospital and Harvard Medical School, Charlestown (M.N., H.Z., S.H., P.P., D.E.S., E.A., F.K.S., R.W.); Donald W. Reynolds Cardiovascular Clinical Research Center on Atherosclerosis at Harvard Medical School, Boston, Mass (M.N., E.A., P.L., R.W.); Department of Cardiology, Massachusetts General Hospital, Boston (D.E.S.); and...
- ORCID
- Venue
- Circulation
- Published
- 2008-01-22
- Volume
- 117
- Issue
- 3
- Pages
- 379-387
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- PMC
- PMC2663426
- OpenAlex
- W2011809692
- Cited by
- 559
- References
- 32
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 17 · 2023: 15 · 2022: 33 · 2021: 15 · 2020: 24 · 2019: 17 · 2018: 25 · 2017: 30 · 2016: 31 · 2015: 30 · 2014: 40 · 2013: 33 · 2012: 55
- FWCI
- 32.74
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- Funders
- University of Washington
- National Heart, Lung, and Blood Institute (U01HL080731, R01HL078641, R00HL094533)
- National Cancer Institute (R24-CA-92782, R24CA092782)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Cardiac Imaging and Diagnostics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- atherosclerosis, macrophages, positron emission tomography, nanoparticles, copper-64, CD68, ApoE-deficient mice, atherosclerotic plaque, multimodal imaging, magnetic resonance imaging, fluorescence imaging, nanoparticle pharmacokinetics
- MeSH terms
- CD68 Molecule, Animals, Apolipoproteins E, Copper Radioisotopes, Inflammation, Macrophages, Microscopy, Sensitivity and Specificity, Antigens, Differentiation, Myelomonocytic, Biomarkers, Antigens, CD, Positron-Emission Tomography, Atherosclerosis, Mice, Nanoparticles
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